The studies presented in this dissertation establish the precise structure and sites of attachment of the covalent linkage that binds heme to CYP4B1, reveal a viable autocatalytic mechanism for its formation, and evaluate ...

The studies that are presented in this dissertation have; (i) established a mechanism by which warfarin dose response is modulated by VKORC1 genotype under optimized conditions for kinetic analysis of human vitamin K epoxide ...

This work is a characterization of small molecule azole-based inhibitor interactions in cytochrome P450 (CYP) using a complement of biophysical methodologies to provide molecular level details of the underappreciated ...

Enzymological paradigms have shifted recently to acknowledge the biological importance of catalytic promiscuity. Detoxification enzymes, such as glutathione transferases, are known to be highly promiscuous. One common ...

In recent years, therapeutic use of engineered particles on the 1-1,000 nm scale has gained popularity; these nanoparticles have been developed for use in drug delivery, gene therapy, vaccine preparation, and diagnostics. ...

Packaging of viral genomes into procapsids by terminase enzymes is conserved in many DNA viruses. Terminases bind to linear concatemers of replicated viral genomes and concomitantly excise (mature) and package a single ...

Mass spectrometry is a powerful proteomics tool. Advancements in instrumentation and data acquisition techniques allow researchers to identify and quantify thousands of proteins from cellular samples in a high throughput ...

Lapatinib was the first orally active dual tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR, ErbB1) and human epidermal receptor 2 (HER2, ErbB2) to be approved by the US Food and Drug Administration ...

A highly sensitive GC NCI/MS assay was developed for midazolam metabolites. The limit of quantitation was 0.3 ng/mL. This assay allowed the determination of kinetic parameters for metabolite formation from in vitro incubations ...

The glutathione S-transferases (GSTs) represent a family of cytosolic enzymes whose primary function is the detoxification of electrophilic chemical species of endogenous and exogenous origin. As described in the introductory ...

Both computational and experimental approaches were used to study cytochrome b$\sb5.$ The goal was to investigate protein dynamics and how they may relate to stability and biological function.Computational studies used ...

As the most abundant isoform of GST in the liver, the GST A1-1 is the major catalyst of detoxification. This isoform is of particular interest because it exhibits an unusually low pKa (∼8.1--8.3) of active site Tyr-9 and ...

Fish oil has been widely studied for its protective effects against heart disease. These effects are attributed to omega-3 PUFA content, which are also found in sea mammals in addition to fish. The mechanism by which ...

Methadone ((R,S)-6-dimethylamino-4, 4-diphenyl-3-heptanone) is a synthetic mu-opioid receptor agonist developed in Germany during World War II as a replacement for morphine. Methadone is currently used to aid in opioid ...

Several disease states and chemical-induced toxicities are mediated through an early mitochondrial dysfunction. A better understanding of the molecular and biochemical events that transpire during such mitochondrial damage ...

Cytochrome b5 (cyt b5 or holo b5) is known as one of the key components in the microsomal cytochrome P450 (CYP) monooxygenase system that metabolizes structurally diverse endogenous and exogenous compounds. It has been ...

A thorough understanding of the mechanisms of cell death could open the door to numerous opportunities for therapeutic modulation. In addition to disease state treatment options, cell death modulation may also have benefit ...

The metabolism of drugs and other xenobiotics normally expediates elimination and detoxification. However, in some instances inert compounds are transformed into potent alkylating or arylating agents capable of eliciting ...